No adverse effects from high doses of felodipine to patients with coronary heart disease.

Although vasodilators may be of value in treating hypertension and heart failure, excessive vasodilation may worsen poststenotic myocardial perfusion in patients with coronary artery disease. In this study, 11 patients with ischemic heart disease were given 0.010, 0.015, and 0.025 mg/min of felodipine, a potent arteriolar dilator, and hemodynamics and myocardial lactate extraction were measured. Plasma concentrations at the three dose levels (D1, D2, and D3) were 11 +/- 4, 22 +/- 5, and 40 +/- 8 nmol/l, respectively. Mean heart rate rose from 61 +/- 13 to 79 +/- 10 beats/min at D3 (p less than 0.01) and mean arterial pressure was reduced from 113 +/- 25 to 86 +/- 13 mmHg (p less than 0.01). There was a marked increase in cardiac index at all three dose levels (p less than 0.05 to p less than 0.01). The systemic vascular resistance was reduced by 47% at D3 and coronary vascular resistance by 44% (both p less than 0.01). Myocardial oxygen consumption was not changed by felodipine. There were three patients with myocardial lactate production both before and after drug administration, but there were no ST-segment shifts or chest pain in any patient. In conclusion, felodipine seems to be a potent vasodilator and deterioration of myocardial metabolic function occurs infrequently. Our results suggest that felodipine can be safely administered even in high doses to patients with severe coronary artery diseases.